Which Constituents Determine the Antioxidant Activity and Cytotoxicity of Garlic? Role of Organosulfur Compounds and Phenolics.

Garlic is a vegetable with numerous pro-health properties, showing high antioxidant capacity, and cytotoxicity for various malignant cells. The inhibition of cell proliferation by garlic is mainly attributed to the organosulfur compounds (OSCs), but it is far from obvious which constituents of garlic indeed participate in the antioxidant and cytotoxic action of garlic extracts. This study aimed to obtain insight into this question by examining the antioxidant activity and cytotoxicity of six OSCs and five phenolics present in garlic. Three common assays of antioxidant activity were employed (ABTS● decolorization, DPPH● decolorization, and FRAP). Cytotoxicity of both classes of compounds to PEO1 and SKOV-3 ovarian cancer cells, and MRC-5 fibroblasts was compared. Negligible antioxidant activities of the studied OSCs (alliin, allicin, S-allyl-D-cysteine, allyl sulfide, diallyl disulfide, and diallyl trisulfide) were observed, excluding the possibility of any significant contribution of these compounds to the total antioxidant capacity (TAC) of garlic extracts estimated by the commonly used reductive assays. Comparable cytotoxic activities of OSCs and phenolics (caffeic, p-coumaric, ferulic, gallic acids, and quercetin) indicate that both classes of compounds may contribute to the cytotoxic action of garlic.

Comparison of Antioxidant and Antiproliferative Effects of Various Forms of Garlic and Ramsons.

Garlic is known to be rich in antioxidants, inhibit the proliferation of various cancer cells, and hamper cancer formation and growth, but various forms of garlic can differ greatly in these respects. This study aimed to compare the antioxidant properties of acetone, ethanol, and aqueous extracts of fresh Polish and Spanish garlic, black and granulated garlic, as well as fresh and dried ramsons. Extracts of black and granulated garlic showed the lowest total antioxidant capacity (TAC). The content of phenolic compounds correlated with TAC measured by ABTS• decolorization and FRAP methods, and with the results of FRAP and DPPH• decolorization assays. Garlic extracts inhibited the proliferation of PEO1 and SKOV3 ovarian cancer cells and, usually to a smaller extent, MRC-5 fibroblasts. PBS extracts of fresh Spanish garlic showed the highest potency for inhibition of proliferation of PEO1 cells (IC50 of 0.71 µg extract dry mass/100 µL medium). No significant correlation was found between the potency for inhibition of proliferation and the content of phenolics or flavonoids, confirming that phenolics are the main determinants of TAC but do not contribute significantly to the antiproliferative effects of garlic.

Enhanced Anti-Proliferative Effect of Carboplatin in Ovarian Cancer Cells Exploiting Chitosan-Poly (Lactic Glycolic Acid) Nanoparticles.

OBJECTIVE: The present article aimed to enhance the therapeutic efficacy of carboplatin (CP) using the formulation of chitosan-poly (lactic glycolic acid) nanoparticles (CS-PLGA NPs). METHODS: Nanoparticles were synthesized by an ionic gelation method and were characterized for their morphology, particle size, and surface potential measurements by TEM and zeta sizer. This study was highlighted for the evaluation of drug entrapment, loading and in vitro drug release capabilities of the prepared nanoparticles by spectrophotometric analysis. The stability study was also conducted after 3 months for their particle size, zeta potential, drug loading and encapsulation efficiencies. Further, ovarian cancer cell line PEO1 was used to evaluate the toxicity and efficacy of nano-formulation by MTT assay. Additionally, the study was evaluated for apoptosis using flow cytometric analysis. RESULTS: The CS-PLGA-CP NPs were uniform and spherical in shape. The particle size and zeta potential of CS-PLGA-CP NPs were measured to be 156 ±6.8 nm and +52 ±2.4 mV, respectively. High encapsulation (87.4 ± 4.5%) and controlled retention capacities confirmed the efficiency of the prepared nanoparticles in a time and dose-dependent manner. The cytotoxicity assay results also showed that CS-PLGA-CP NPs have a high efficiency on PEO1 cells compared to the free drug. The flow cytometric result showed 64.25% of the PEO1 cells were apoptotic, and 8.42% were necrotic when treated with CS-PLGA-CP NPs. CONCLUSION: Chitosan-PLGA combinational polymeric nanoparticles were not only steady but also non-toxic. Our experiments revealed that the chitosan-PLGA nanoparticles could be used as a challenging vehicle candidate for drug delivery for the therapeutic treatment of ovarian cancer.

Extracts of Common Vegetables Inhibit the Growth of Ovary Cancer Cells.

There is recent interest in a diet that can be recommended for patients suffering from cancer. In this respect, the effects were studied of the extracts of several common fruits, herbs and vegetables on the viability of two human ovary cancer cell lines (SKOV-3 and PEO1) in vitro. Normal human MRC-5 fibroblasts were used as a control cell line. The extracts of garlic, horseradish and curly kale as well as green and black tea were the most effective in lowering the viability of ovarian cancer cells, while not affecting the viability of MRC-5 fibroblasts. Except for garlic and horseradish, the cytotoxic effects of the extracts correlated with their polyphenol content. The examination of changes in the content of ATP and glutathione, in the level of reactive oxygen species, mitochondrial potential and mitochondrial mass did not show a consistent pattern, suggesting that various extracts may act via different mechanisms. Although the extracts' toxicity to cells in vitro is a first and direct suggestion concerning their possible anticancer effects in vivo, these results point to potential vegetable candidates to become diet components recommended for ovary cancer patients.

Twinkle-Associated Mitochondrial DNA Depletion.

BACKGROUND: Autosomal recessive mutations in the nuclear Twinkle (C10orf2) gene cause a mitochondrial DNA depletion syndrome (MDS) characterized by early onset hepatoencephalopathy. METHODS: We report a severe, early onset encephalopathy and multisystem failure case caused by novel recessive Twinkle gene mutations. Patient clinical, laboratory, and pathological features are reported and Twinkle-associated MDS literature reviewed. RESULTS: Typical presentation includes symptom onset before age six months, failure to thrive, psychomotor regression, epileptic encephalopathy, sensory axonal neuropathy, cholestatic liver dysfunction, and occasionally, renal tubulopathy, movement disorders, and ophthalmoplegia. Death is typical before age four years. CONCLUSIONS: In the differential diagnosis of early onset encephalopathy and multisystem failure, MDS should be considered.

Twinkle mutation in an Italian family with external progressive ophthalmoplegia and parkinsonism: a case report and an update on the state of art.

The objective is to describe the clinical phenotype and genetic basis of a family with autosomal dominant progressive external ophthalmoplegia and parkinsonism with a Twinkle mutation. The proband, an 82 years old female, reported since childhood bilateral eyelid ptosis, ophthalmoplegia, sensorineural hypoacusis, mild depression since she was 45, with a positive familiar anamnesis of eyelid ptosis (father, two sisters and a son). She developed mild bilateral parkinsonism with a moderate clinical response to levodopa. The (123)I-FP-CIT SCAN evidenced a marked bilateral putaminal reduction and moderate caudate uptake reduction. Her 79 years old sister reported eyelid ptosis since she was 45 with ophthalmoplegia and developed a mild bilateral rest and postural tremor with moderate right arm plastic hypertonia when she was 76. The parkinsonism was confirmed with (123)I-FP-CIT SCAN. One of the two sons presented eyelid ptosis since he was 30 years old, with peripheral neuropathy with biopsy evidence of myopathy. We identified a G1750A mutation in the c10orf2 gene in the three patients. Mitochondrial dysfunction has been implicated in the pathogenesis of sporadic, idiopathic Parkinson disease (PD). In some cases, mitochondrial DNA primary genetic abnormalities or more commonly secondary rearrangements due to polymerase gamma (POLG) gene mutation can directly cause parkinsonism. Parkinsonism has been reported as a rare symptom associated to Twinkle (c10orf2). Parkinsonism has to be investigated in patients with PEO with analysis of Twinkle mutation.

Subacute peripheral and optic neuropathy syndrome with no evidence of a toxic or nutritional cause.

BACKGROUND: The syndrome of subacute simultaneous peripheral neuropathy and bilateral optic neuropathy is known to occur in tropical countries, probably due to malnutrition or toxicity, but not often seen in developed countries. We report seven patients in London who were not malnourished or alcoholic, and in whom no clear cause was found. METHODS: We retrospectively reviewed the case notes and arranged some further investigations. RESULTS: All patients developed peripheral and bilateral optic neuropathy within 6 months. Patients were aged 30-52, and all of Jamaican birth and race but lived in the UK. Most had subacute, painful ataxic sensory axonal neuropathy or neuronopathy, some with myelopathy. Nerve conduction studies revealed minor demyelinating features in two cases. The optic neuropathy was symmetrical, subacute and monophasic, usually with marked reduction in visual acuity. CSF protein concentration was usually elevated but other laboratory investigations were normal. Patients showed only modest improvement at follow-up. CONCLUSION: These patients share a common clinical and electrophysiological phenotype, age, ethnicity and elevated CSF protein, but otherwise normal laboratory investigations. The syndrome is a cause of significant morbidity in young people. The cause remains uncertain despite thorough investigation.